Patent application WO2006/108558 discloses a device for dosing and dry nebulization of nebulizable material chosen from a group comprising anti-infective agents and immunomodulators, comprising a nebulization channel, which has a first attachment piece and a second attachment piece, and a source of compressed carrier gas connected to the first attachment piece via a valve for the purpose of sending a carrier gas pressure pulse into the nebulization channel. The device is characterized in that between the first attachment piece and second attachment piece, and above the nebulization channel, a reservoir open only towards the nebulization channel, which contains the nebulizable material, is connected to the nebulization channel such that it is gas-tight with respect to the environment, and that, when the valve is closed, a pressure compensation takes place in the nebulization channel and in the reservoir. The invention also relates to a method for dosing and dry nebulization of such a nebulizable material by means of such a device.
However this device, intended for use in hospitals, requires an external source of compressed gas, and is therefore large and bulky.
Patent application WO2011/080761A1 requires coordination of breathing and activation, and both it and US2010/0300440A1 deliver the medicament via the mouth.
Another device of prior art, disclosed in PCT application no. PCT/IL2011/00702, is a nasal substance delivery device, wherein the substance is delivered to the nasal cavity employing either drinking or breathing to actuate the device.
Another device of the prior art, disclosed in U.S. Pat. No. 7,806,117 is a peroral powder delivery device having a capsule holder for loading the capsule into a body, the capsule holder attached so as to be capable of advancing into and retracting from the inside of the body. The body has a cutter blade to make holes on both ends of the capsule as it advances into the body while being held by the capsule holder. The body also has first and second air passageways having connection ports in communication with the holes in the capsule loaded in the body. The first air passageway has an inhaling port for inhaling the peroral powder in the capsule and the second air passageway has a suction valve that opens by the inhaling force from an inhaling port introducing air into the capsule.
However, the device of U.S. Pat. No. 7,806,117 differs significantly from the present device. Firstly, it is incapable of delivering the dose entrained in a predetermined fixed volume of air, moving with a well-defined speed (under a predetermined pressure). The volume of air in which the peroral powder is entrained and the speed of the air depend on the volume inspired by the user and the rapidity with which the user inhales, both of which differ significantly between, for example, men and women, adults and children, young people and elderly people, and healthy people and those with breathing difficulties.
Furthermore, the device of U.S. Pat. No. 7,806,117 is intended to deliver medication to the mouth (peroral delivery), not to the nose. If the device were modified for nasal delivery by reshaping the mouthpiece into a nosepiece, it would remain unlike the present device. For example, unlike the present device which provides a fixed pressure and air speed, the suction pressure and, therefore, the aid speed driving air flow through the peroral powder and into the nasal passages would be the suction pressure and air speed of the user's inhalation, a pressure and speed that will differ significantly between, for example, adults and children, young people and elderly people, and healthy people and those with breathing difficulties. Similarly, unlike the present device which provides a fixed volume of gas or air, the volume of air inhaled will differ significantly between, for example, men and women, adults and children, young people and elderly people, and healthy people and those with breathing difficulties.
If the device of U.S. Pat. No. 7,806,117 were to be modified to include a second tube, with one tube emplaced in the mouth and the second emplaced in a nostril, oral suction would result in air flowing from the nostril towards the mouth, rather than the desired direction, from the capsule towards the nostril. Inhalation simultaneous with oral suction would result in part of the peroral powder entering the nostril and part entering the mouth, with the fraction entering the nostril depending on the relative strengths of the suction and the inhalation, very far from the controlled delivery of the present device, with the entirety of the dose entering the nostril at a well-defined speed, entrained in a well-defined volume of air.
One of the major advantages of the present invention is the use of a constant, accurate and large volume of air.
Another device of the prior art, disclosed in U.S. Pat. No. 7,722,566 discloses a device that delivers a powdery medicine for a nasal cavity includes positioning guides that cause a capsule to slide as far as a predetermined position and are provided on the side of cutters to make holes on both ends of the capsule provided between the connection port on the side of a nozzle that sprays the powdery medicine into the nasal cavity. The device further includes a connection port on the side of a pump that supplies spray air to the nozzle in order to make the size of the holes made on both ends of the capsule constant, wherein a distance between the connection ports is made shorter than a distance between blade tips of the cutters.
This device differs significantly from the device of the present invention in being a one-step device, wherein compression of an elastic-walled space (the “pump”) causes air to flow through the device, through a capsule containing medicament, and into both nostrils. The volume of air delivered by the device of U.S. Pat. No. 7,722,566 is more consistent than the volume of air delivered in U.S. Pat. No. 7,806,117, since it will be, in practice, a relatively consistent fraction of the volume of the pump, the fraction depending on the strength of the user and the physical properties of the elastic walls of the pump. Similarly, the air pressure delivering the air to the nostril and the air speed will be more consistent than U.S. Pat. No. 7,806,117, as they also depend on the strength of the user and the physical properties of the pump. However, the device of U.S. Pat. No. 7,722,566 differs from the present device in that, in the present device, none of the air speed, air volume or air pressure depends on the abilities of the user.
In addition, unlike the present device, the length of time over which the dose is delivered in U.S. Pat. No. 7,722,566 depends on how fast the user squeezes the pump. In the present device, the length of time over which the dose is delivered depends solely on the physical properties, such as shape and size, of the predetermined interior of the device.
Furthermore, the device of U.S. Pat. No. 7,722,566 is a one-step device—the user compresses the pump and the contents of the capsule are delivered. The present device is a two-step device, where the air chamber (the closest equivalent of the pump in U.S. Pat. No. 7,722,566) is charged with a fixed volume of air during a charging step. In an activation step, a valve is opened, the capsule is opened, and the contents of the air chamber are delivered to the nostril, ensuring that air pressure, air speed, air volume and time of delivery are completely consistent in in every activation.
Devices of prior art intended to deliver substances to the nasal passages are most commonly employed to deliver drugs and medicaments locally to the nasal cavity, to the lungs and to the blood, via the lower sections of the nasal passages. Difficulties have been experienced in delivering the substances to the central and upper sections of the nasal passages, such as the middle and upper turbinates. From the middle and upper turbinates, it is possible to deliver drugs to the brain, as pathways in the middle and upper turbinates can deliver medicaments across the thin ethmoid bone separating the nasal passages from the brain, bypassing the blood-brain barrier and allowing the passage of large or hydrophilic molecules that are unable to pass into the cerebrospinal fluid via the blood. The nasal route also enables delivery to the brain of substances that would otherwise be degraded by the digestive system and first pass metabolism in the liver if administered by the oral route. Also, the nasal route could serve as an alternative to parenteral route with greater user compliance, for the delivery of therapeutics to the brain and other tissues as lungs, heart and blood.
Many devices of prior art deliver the desired substance via a mist, usually in a liquid or gas carrier, with all the attendant disadvantages thereof. These include the degradation of medicaments during storage; unwanted interactions of drug with carrier; and the possibility of allergic reactions to the carrier. Also, those delivery applicators usually result in the presence of large droplets which are incapable of reaching the turbinates and possess limited absorption capability and wide dispersions of droplet size, which make control of deposition location difficult and cause variability in absorption rates and characteristics.
A further disadvantage of devices wherein the substance is entrained within an inert carrier (i.e., the pressurized gas) is that the volume and weight of the carrier is substantially larger than the volume and weight of the medicament.
Carrier-free delivery devices have depended on accurate control of breathing by the user, usually involving a prolonged inspiration, often accompanied by coordination of activation with inhalation. Prolonged inhalation is difficult for many patients, such as asthmatics, and coordination of inhalation with activation can be difficult, both for asthmatics and for small children. Also, in most cases, there is a straight correlation between the strength of the inhalation and the amount of medicament delivered.
Other carrier-free dry mist devices either require significant force to operate, beyond the strength of children and of weaker adults, or require a source of compressed gas so that they are large and bulky and are not easily transportable.
It is therefore a long felt need to provide a device that does not require coordination of breathing with activation, that does not require long or deep inspiration, that ensures reproducible and precise dose delivery in every activation and that is capable of delivering either medicaments in a carrier or carrier-free medicaments to the desired turbinates in the nose including the upper turbinates and, optionally, from there to the brain.